Modulator role of Caveolin-1 in shear stress-induced NOS inhibitor?sensitive and insensitive NO activity in the isolated perfused rat mesenteric bed

In this study, it was investigated that the probable modulator role of Caveolin-1 in shear stress- induced NOS inhibitors-sensitive and insensitive NO activity in the isolated perfused rat mesenteric bed. In the control, the pressure of mesenteric bed was increased depending on cumulative phenylephrine,?1 adrenoceptor agonist. Pretreatment of the tissue with MßCD, a cholesterole depletant, augmented the pressure increased by phenylephrine. Also MßCD-treatment of the tissue disrupted the structural integrity of caveolea as demonstreated by the reduction of caveolea invaginations at the endothelial membrane surface which was clearly visible as revealed by electron microscopy. However, the level of eNOS was increased in the tissue treated with MßCD when compared to untreated. NOS inhibitors, L-NA or L-NAME, and endothelium denudation increased the pressure more potently aganist the control. However pretreatment of MßCD inhibited the contractions in the endothelium ?denuded tissue.In the MßCD-pretreated tissue, increament in the pressure by the presence of NOS inhibitors or NOS inhibitors plus NO inhibitor hydroxocobalamine (HC), was significantly lower than that of observed with MßCD-untreated groups.These findings suggest that 1- NO release evoked by vasoconstriction has two components which are NOS inhibitor-sensitive and ?insensitive forms, 2- they may have important roles in modulation of vascular bed contraction, 3- this modulation is associated with cholesterol-rich membrane caveolaes. 4- the distruption of the membrane caveolae with MßCD augmented the pressure induced by phenylephrine. 5- this augmentation in the pressure may be due to the decreased levels of NOS which localized by caveolin-1, 6- the diminished levels caveola associated with the reduction in both NOS inhibitors-sensitive and ?insensitive NO activity.